Project Summary/Abstract Nanoparticle-Stabilized Capsules as Drug Delivery Systems Nanoparticle-stabilized capsules (NPSCs) provide a modular platform for the creation of delivery vehicles featuring a high carrier to payload ratio. In recent research, we have developed an alternative mode of NPSC stabilization that relies on stabilization of the capsule through supramolecular interactions between the nanoparticle shell and complementary hydrophobic "oil" components. Using this method, we have been able to produce nanocapsules featuring diameters as small as 100 nm. In our proposed research we will fabricate capsules based on this design and perform cell culture studies to determine their viability in delivery applications. Our proposed program features two Aims: Aim 1: We will fabricate NPSCs, focusing on the control of capsule size, stability, and functionalization. We will control particle size and stability through tailoring of particle-droplet and particle-particle interactions, as well as stabilize the NPSC shell through environmentally-responsive crosslinking. Aim 2: The efficacy of uncrosslinked and crosslinked particles for drug delivery will then be determined in a range of cell lines. Concurrently, we will determine the mechanism of payload release and determine the efficiency of drug delivery. We will also determine the efficiency of targeting using folate, RGD, galactose, transferrin and tamoxifen targeting. The goal of this two-year R21 grant is to develop strategies for the creation of nanometer-scale NPSCs and perform cell culture studies demonstrating the stability of these systems and their capabilities in drug delivery. These studies will provide proof-of-concept validation that will provide the foundation for animal model studies in future funding periods. PUBLIC HEALTH RELEVANCE: Project Narrative: Significance: Nanoparticle-stabilized capsules present a new means of delivering therapeutics to specific location in the body such as tumors or organs. In our proposed research we will develop new strategies to fabricate and tune particles for delivery applications, providing potential access to new therapeutic strategies.